The overall goal of the proposed study is to determine the effects of substance use (abuse/dependence) disorder (SUD) comorbidity on the rate, time and degree of recovery and two-year outcome in patients hospitalized with a first-episode of mania after adjusting for adequacy of treatment. Factors that are known to influence comorbidity in mania such as family history and presence of mixed episodes will be evaluated. All admissions to McLean Hospital are screened to obtain a cohort of 231 (101 recruited and followed for 24 months + 37 to be recruited before funding starts and followed for 24 months + 93 to be recruited and followed for 24 months during the funding period) first-episode manic patients. The diagnostic interview for genetic studies (DIGS) and. the Structured Interview for the diagnosis of DSM-III-R Personality Disorder (SIDP-R) are administered during the index hospitalization and at two years in order to assess stability of the diagnosis. Available first-degree relatives are interviewed with the DIGS and the Family Interview for Genetic Studies (FIGS). All diagnoses including comorbid disorders will be arrived at by a best-estimate procedure. Patients arc rated weekly during the Index hospitalization with symptom rating scales. After discharge, patients are rated every six months to assess recovery, relapse and psychosocial adjustment. Treatment will not be under the control of the investigators but pharmacological and other aspects of clinical management will be carefully documented and included in the analysis. This proposal represents a continuation and refinement of the McLean First-Episode Mania Project whose funding by an NIMH RO3 grant and a NARSAD young investigator award ended on 1131194. At the end of five years, we will be able to obtain follow-up information on 231 first- episode manic patients (including the subjects currently being followed).